The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: a GRADE-assessed systematic review and meta-analysis of randomised controlled trials.

Curcumin is a phytocompound found in the root of turmeric, a common herbal ingredient in many Asian cuisines. The compound contains anti-inflammatory activity, which is mediated through an upregulation of adiponectin and reduction of leptin. Results of randomised controlled trials (RCT) have shown that the effects of curcumin on adipokines are conflicting. Therefore, the current systematic review and meta-analysis of RCT were conducted with the aim of elucidating the role of curcumin supplementation on serum adiponectin and leptin. The search included PubMed, Embase, Cochrane Library, Scopus, Web of Science and Google Scholar from inception to August 2023. For net changes in adipokines, standardised mean differences (SMD) were calculated using random effects models. Thirteen RCT with fourteen treatment arms were eligible for inclusion in this meta-analysis. Curcumin supplementation was effective in increasing serum adiponectin (SMD = 0·86, 95 % CI (0·33, 1·39), P < 0·001; I2 = 93·1 %, P < 0·001) and reducing serum leptin (SMD = -1·42, 95 % CI (-2·29, -0·54), P < 0·001; I2 = 94·7 %, P < 0·001). In conclusion, curcumin supplementation significantly increased circulating adiponectin and decreased leptin levels in adults.

BuOH fraction of Salix Babylonica L. extract increases pancreatic beta-cell tumor death at lower doses without harming their function.

Salix babylonica L. is a species of the willow tree. Insulinoma is a tumor originating from pancreatic beta cells. This study aims to research the effect of different fractions of Salix babylonica L. leaf extract on INS-1 cells for treating pancreatic tumors. Cell death occurred at lower doses in the EtOAc fraction. The cells are functional in the BuOH fraction but not in EtOAc and H2O fractions. The EtOAc fraction has a higher percentage of necrosis and ROS. INS1, INS2, and AKT gene expressions in the H2O fraction, GLUT2, IR, HSP70 gene expressions, and WNT4 protein levels increased in the BuOH fraction. HSP90 gene expression, Beta-actin, GAPDH, insulin, HSP70, HSP90, HSF1, Beta-Catenin, and WNT7A protein levels were decreased, while IR immunolabelling intensity increased in both fractions. Ca+2, K+, Na+, and CA-19-9 in the cell, Ca+2 and K+ in secretion increased. The secondary metabolites in the EtOAc fraction cause more damage in INS-1 cells. Since the water fraction also causes the cells to die in high doses, cell function is damaged. The secondary metabolites in the BuOH fraction kill INS-1 cells with less damage. This makes the BuOH fraction of Salix babylonica L. more valuable.

Coating with cationic inulin enhances the drug release profile and in vitro anticancer activity of lecithin-based nano drug delivery systems.

Core-shell structured lipidic nanoparticles (LNPs) were developed using lecithin sodium acetate (Lec-OAc) ionic complex as a core unit and quaternized inulin (QIn) as the shell part. Inulin (In) was modified using glycidyl trimethyl ammonium chloride (GTMAC) as a positively charged shell part and used for coating the negatively surface charged Lec-OAc. The critical micelle concentration (CMC) of the core was determined as 1.047 × 10-4 M, which is expected to provide high stability in blood circulation as a drug-carrying compartment. The amounts of curcumin (Cur) and paclitaxel (Ptx) loaded to LNPs (CurPtx-LNPs), and quaternized inulin-coated LNPs (Cur-Ptx-QIn-LNPs) were optimized to obtain mono-dispersed particles with maximum payload. The total amount of 2.0 mg of the drug mixture (1 mg Cur and 1 mg Ptx) was the optimized quantity for QIn-LNPs and CurPtx-QIn-LNPs due to the favorable physicochemical properties determined by dynamic light scattering (DLS) studies. This inference was confirmed by differential scanning calorimeter (DSC), and Fourier-transform infrared (FT-IR). SEM and TEM images clearly revealed the spherical shapes of LNPs and QIn-LNPs, and QIn covered the LNPs completely. The cumulative release measurements of Cur and Ptx from CurPtx-QIn-LNPs, along with the kinetic studies, showed a significant decrease in the release period of drug molecules with the effect of the coating. At the same time, Korsmeyer-Peppas was the best diffusion-controlled release model. Coating of the LNPs with QIn increased the cell-internalization of NPs to the MDA-MB-231 breast cancer cell lines, resulting in a better toxicity profile than the empty LNPs.

Levan enhanced the NF-κB suppression activity of an oral nano PLGA-curcumin formulation in breast cancer treatment.

Chemoresistance (CR) is one of the reasons why chemotherapy agents like Gemcitabine (GMC) remain insufficient in healing breast cancer. Activation of Nuclear Factor-kappa B (NF-κB) during chemotherapy is known as an important factor in the development of CR. The hydrophobic polyphenol curcumin is shown to inhibit NF-κB and hence CR. The aim of this work was to increase the poor bioavailability of curcumin by loading it into the nano-micelles made of Poly (Lactide-co-Glycolide) (PLGA) and levan, where levan as a natural fructose homopolymer makes the nano-micelle more stable and increases its uptake using the fructose moieties. In this study, a PLGA-levan-curcumin formulation (PLC) was designed and characterized. The size was measured as 154.16 ± 1.45 nm with a 67.68% encapsulation efficiency (EE%). The incorporation between the components was approved. Levan made the nano-micelles stable for at least three months, increased their uptake, and led to a 10,000-fold increase in the solubility of curcumin. The enhanced bioavailability of curcumin reduced the NF-κB levels elevated by GMC, both in vitro and in vivo. The PLC showed a complete tumor treatment, while GMC only showed a rate of 52%. These point to the great potential of the PLC to be used simultaneously with chemotherapy.

Anticholinesterase and Antioxidant Activities of Natural Abietane Diterpenoids with Molecular Docking Studies.

BACKGROUND: Alzheimer's Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes. OBJECTIVE: Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity. METHODS: In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine. RESULTS: Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 µM) and AChE (33.21 µM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 µM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests. CONCLUSION: Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD.

Inhibition of Amyloid ß Aggregation Using Optimized Nano-Encapsulated Formulations of Plant Extracts with High Metal Chelator Activities.

BACKGROUND: The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid ß (Aß) and consequently, the progression of Alzheimer's disease (AD) is well established. OBJECTIVE: Development of non-toxic metal chelators is an emerging era in the treatment of AD, in which complete success has not been fully achieved. The purpose of this study was to determine plant extracts with high metal chelator and to encapsulate them in nano-micellar systems with the ability to pass through the Blood Brain Barrier (BBB). METHODS: Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2 chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating property. RESULTS: Verbascum flavidum aqueous extract was found as the most active sample, incubation of which, with Aß before and after metal-induced aggregation, resulted in successful inhibition of aggregate formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The same results were obtained using ApoEPLGA. CONCLUSION: An optimized metal chelator nano-formulation with BBB penetrating ability was prepared and presented for further in-vivo studies.

Indole alkaloids from Vinca major and V. minor growing in Turkey.

A new indole alkaloid, 11-hydroxypolyneuridine, was isolated from Vinca major subsp. major L. and the known indole alkaloids vallesiachotamine and isovallesiachotamine from Vinca minor L. This is the first report on the alkaloids of both Vinca species growing in Turkey; vallesiachotamine and isovallesiachotamine were isolated from a Vinca species for the first time. V. minor may be considered as a new source for these two alkaloids due to their occurrence in high amount in the aerial parts of the plant. The alkaloid extracts of the two Vinca species were found to have high lipid peroxidation inhibitory and DPPH radical scavenging activities. Anticholinesterase activity of the extracts was also very strong.

Antioxidant phenolic compounds from the leaves of Erica Arborea (Ericaceae).

Reversed-phase HPLC analyses of the methanol extract of the leaves of Erica arborea afforded a novel phenylpropanoid glucoside, named ericarborin, together with five flavonoids, dihydromyricetin 3-O-alpha-L-rhamnopyranoside, quercetin 3-O-beta-D-glucopyranoside, quercetin 3-O-alpha-L-rhamnopyranoside, apigenin 7-O-beta-D-glucopyranoside and apigenin 7-O-beta-D-(6-O-acetyl-glucopyranoside). While the structure of ericarborin was determined by extensive 1D and 2D NMR analyses, the structures of all known flavonoids were determined by direct comparison of their spectroscopic data with respective literature data. The antioxidant properties of these compounds were assessed by the DPPH assay. The chemotaxonomic significance of these phenolic compounds has been discussed.

Antioxidant activity of Erica arborea.

The antioxidant properties of the methanol extract of leaves and flowers of Erica arborea and the ethyl acetate, butanol and water soluble fractions were investigated. The ethyl acetate extract was found to be the richest for phenolic and flavonoid content which showed the highest antioxidant activity.